Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1979 Aug;64(2):381–384. doi: 10.1172/JCI109472

Gangliosides sensitize unresponsive fibroblasts to Escherichia coli heat-labile enterotoxin.

J Moss, S Garrison, P H Fishman, S H Richardson
PMCID: PMC372129  PMID: 222809

Abstract

Chemically transformed mouse fibroblasts did not raise their cyclic AMP level in response to Escherichia coli heat-labile enterotoxin. These fibroblasts did, however, incorporate exogenous mono-, di-, and trisialogangliosides. After the uptake of monosialoganglioside galactosyl-N-acetylgalactosaminyl-[N-acetylneuraminyl]-galactosylglucosylceramide (GM1), the cells responded to E. coli heat-labile enterotoxin. The di- and trisialogangliosides were considerably less effective. GM1, the putative cholera toxin (choleragen) receptor, has been implicated previously as the receptor for E. coli heat-labile enterotoxin based on the ability of the free ganglioside to inhibit the effects of toxin. This investigation establishes that the ganglioside, when incorporated into fibroblasts, serves a functional role in mediating the responsiveness to the toxin.

Full text

PDF
381

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cassel D., Pfeuffer T. Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2669–2673. doi: 10.1073/pnas.75.6.2669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Clyman R. I., Blacksin A. S., Sandler J. A., Manganiello V. C., Vaughan M. The role of calcium in regulation of cyclic nucleotide content in human umbilical artery. J Biol Chem. 1975 Jun 25;250(12):4718–4721. [PubMed] [Google Scholar]
  3. Evans D. J., Evans D. G., Gorbach S. L. Polymyxin B-Induced Release of Low-Molecular-Weight, Heat-Labile Enterotoxin from Escherichia coli. Infect Immun. 1974 Nov;10(5):1010–1017. doi: 10.1128/iai.10.5.1010-1017.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Evans D. J., Jr, Chen L. C., Curlin G. T., Evans D. G. Stimulation of adenyl cyclase by Escherichia coli enterotoxin. Nat New Biol. 1972 Apr 5;236(66):137–138. doi: 10.1038/newbio236137a0. [DOI] [PubMed] [Google Scholar]
  5. Finkelstein R. A., Vasil M. L., Jones J. R., Anderson R. A., Barnard T. Clinical cholera caused by enterotoxigenic Escherichia coli. J Clin Microbiol. 1976 Mar;3(3):382–384. doi: 10.1128/jcm.3.3.382-384.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fishman P. H., Brady R. O., Bradley R. M., Aaronson S. A., Todaro G. J. Absence of a specific ganglioside galactosyltransferase in mouse cells transformed by murine sarcoma virus. Proc Natl Acad Sci U S A. 1974 Feb;71(2):298–301. doi: 10.1073/pnas.71.2.298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fishman P. H., Moss J., Vaughan M. Uptake and metabolism of gangliosides in transformed mouse fibroblasts. Relationship of ganglioside structure to choleragen response. J Biol Chem. 1976 Aug 10;251(15):4490–4494. [PubMed] [Google Scholar]
  8. Gill D. M., Evan D. J., Jr, Evans D. G. Mechanism of activation adenylate cyclase in vitro by polymyxin-released, heat-labile enterotoxin of Escherichia coli. J Infect Dis. 1976 Mar;133 (Suppl):103–107. doi: 10.1093/infdis/133.supplement_1.s103. [DOI] [PubMed] [Google Scholar]
  9. Gill D. M. Involvement of nicotinamide adenine dinucleotide in the action of cholera toxin in vitro. Proc Natl Acad Sci U S A. 1975 Jun;72(6):2064–2068. doi: 10.1073/pnas.72.6.2064. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gill D. M., Meren R. ADP-ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. Proc Natl Acad Sci U S A. 1978 Jul;75(7):3050–3054. doi: 10.1073/pnas.75.7.3050. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gorbach S. L., Kean B. H., Evans D. G., Evans D. J., Jr, Bessudo D. Travelers' diarrhea and toxigenic Escherichia coli. N Engl J Med. 1975 May 1;292(18):933–936. doi: 10.1056/NEJM197505012921801. [DOI] [PubMed] [Google Scholar]
  12. Gyles C. L. Relationships among heat-labile enterotoxins of Escherichia coli and Vibrio cholerae. J Infect Dis. 1974 Mar;129(3):277–283. doi: 10.1093/infdis/129.3.277. [DOI] [PubMed] [Google Scholar]
  13. Hewlett E. L., Guerrant R. L., Evans D. J., Jr, Greenough W. B., 3rd Toxins of Vibrio cholerae and Escherichia coli stimulate adenyl cyclase in rat fat cells. Nature. 1974 May 24;249(455):371–373. doi: 10.1038/249371a0. [DOI] [PubMed] [Google Scholar]
  14. Holmgren J. Comparison of the tissue receptors for Vibrio cholerae and Escherichia coli enterotoxins by means of gangliosides and natural cholera toxoid. Infect Immun. 1973 Dec;8(6):851–859. doi: 10.1128/iai.8.6.851-859.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hynie S., Rasková H., Sechser T., Vanecek J., Matejovská D., Matejovská V., Treu M., Polák L. Stimulation of intestinal and liver adenyl cyclase by enterotoxin from strains of Escherichia coli enterpathogenic for calves. Toxicon. 1974 Mar;12(2):173–179. doi: 10.1016/0041-0101(74)90242-6. [DOI] [PubMed] [Google Scholar]
  16. Kantor H. S., Tao P., Gorbach S. L. Stimulation of intestinal adenyl cyclase by Escherichia coli enterotoxin: comparison of strains from an infant and an adult with diarrhea. J Infect Dis. 1974 Jan;129(1):1–9. doi: 10.1093/infdis/129.1.1. [DOI] [PubMed] [Google Scholar]
  17. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  18. Merson M. H., Morris G. K., Sack D. A., Wells J. G., Feeley J. C., Sack R. B., Creech W. B., Kapikian A. Z., Gangarosa E. J. Travelers' diarrhea in Mexico. A prospective study of physicians and family members attending a congress. N Engl J Med. 1976 Jun 10;294(24):1299–1305. doi: 10.1056/NEJM197606102942401. [DOI] [PubMed] [Google Scholar]
  19. Moss J., Fishman P. H., Manganiello V. C., Vaughan M., Brady R. O. Functional incorporation of ganglioside into intact cells: induction of choleragen responsiveness. Proc Natl Acad Sci U S A. 1976 Apr;73(4):1034–1037. doi: 10.1073/pnas.73.4.1034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Moss J., Manganiello V. C., Vaughan M. Hydrolysis of nicotinamide adenine dinucleotide by choleragen and its A protomer: possible role in the activation of adenylate cyclase. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4424–4427. doi: 10.1073/pnas.73.12.4424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Moss J., Richardson S. H. Activation of adenylate cyclase by heat-labile Escherichia coli enterotoxin. Evidence for ADP-ribosyltransferase activity similar to that of choleragen. J Clin Invest. 1978 Aug;62(2):281–285. doi: 10.1172/JCI109127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Moss J., Vaughan M. Mechanism of action of choleragen. Evidence for ADP-ribosyltransferase activity with arginine as an acceptor. J Biol Chem. 1977 Apr 10;252(7):2455–2457. [PubMed] [Google Scholar]
  23. Nalin D. R., McLaughlin J. C. Effects of choleragenoid and glucose on the response of dog intestine to escherichia coli enterotoxins. J Med Microbiol. 1978 May;11(2):177–186. doi: 10.1099/00222615-11-2-177. [DOI] [PubMed] [Google Scholar]
  24. Pacuszka T., Duffard R. O., Nishimura R. N., Brady R. O., Fishman P. H. Biosynthesis of bovine thyroid gangliosides. J Biol Chem. 1978 Aug 25;253(16):5839–5846. [PubMed] [Google Scholar]
  25. Pierce N. F. Differential inhibitory effects of cholera toxoids and ganglioside on the enterotoxins of Vibrio cholerae and Escherichia coli. J Exp Med. 1973 Apr 1;137(4):1009–1023. doi: 10.1084/jem.137.4.1009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Sack R. B. Human diarrheal disease caused by enterotoxigenic Escherichia coli. Annu Rev Microbiol. 1975;29:333–353. doi: 10.1146/annurev.mi.29.100175.002001. [DOI] [PubMed] [Google Scholar]
  27. Zenser T. V., Metzger J. F. Comparison of the action of Escherichia coli enterotoxin on the thymocyte adenylate cyclase-cyclic adenosine monophosphate system to that of cholera toxin and prostaglandin E1. Infect Immun. 1974 Sep;10(3):503–509. doi: 10.1128/iai.10.3.503-509.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. van Heyningen S. Cholera toxin. Biol Rev Camb Philos Soc. 1977 Nov;52(4):509–509. doi: 10.1111/j.1469-185x.1977.tb00858.x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES